Nicotinic acetylcholine receptors are ligand-regulated ion channels which are of importance in neurotransmission in the animal kingdom. The binding of acetylcholine or other agonists to the receptor induces a transient opening of the channel and allows cations to flow through. It is assumed that a receptor consists of five subunits which are grouped around a pore. Each of these subunits is a protein which consists of an extracellular N-terminal moiety followed by three transmembrane regions, an intracellular moiety, a fourth transmembrane region and a short extracellular C-terminal moiety (Changeux et al. 1992).
Acetylcholine receptors are especially well investigated in vertebrates. In this context, three groups can be distinguished on the basis of their anatomical location and their functional properties (conducting properties of the channel, desensitization, and sensitivity towards agonists and antagonists and also towards toxins such as α-bungarotoxin). The classification correlates with the molecular composition of the receptors. There are heterooligomeric receptors having the subunit composition α2βγδ, which are found in muscle (Noda et al. 1982, Claudio et al. 1983, Devillers-Thiery et al. 1983, Noda et al. 1983a, b), heterooligomeric receptors which contain subunits from the α2-α6 and β2-β4 groups and which are found in the nervous system (Wada et al. 1988, Schoepfer et al. 1990, Cockcroft et al. 1991, Heinemann et al. 1997), and also homooligomeric receptors which contain subunits from the α7-α9 group and which are likewise found in the nervous system (Lindstrom et al. 1997, Elgoyhen et al. 1997). This classification is also supported by an examination of the relatedness of the gene sequences of the different subunits. Typically, the sequences of functionally homologous subunits from different species are more similar to each other than are sequences of subunits which are from different groups but from the same species. Thus, the rat muscle α subunit, for example, exhibits 78% amino acid identity and 84% amino acid similarity with that of the electric ray Torpedo californica but only 48% identity and 59% similarity with the rat α2 subunit (heterooligomeric, neuronal) and 36% identity and 45% similarity with the rat α7 subunit (homooligomeric, neuronal). Furthermore, the gene sequences of all the known acetylcholine receptor subunits are to a certain extent similar not only to each other but also to those of some other ligand-regulated ion channels (e.g. the serotonin receptors of the 5HT3 type, the GABA-regulated chloride channels and the glycine-regulated chloride channels). It is therefore assumed that all these receptors are descended from one common precursor and they are classified into one supergene family (Ortells et al. 1995).
In insects, acetylcholine is the most important excitatory neurotransmitter of the central nervous system. Accordingly, acetylcholine receptors can be detected electro-physiologically in preparations of insect central nervous system ganglia. The receptors are detected both in postsynaptic and presynaptic nerve endings and in the cell bodies of interneurones, motor neurones and modulatory neurones (Breer et al. 1987, Buckingham et al. 1997). Some of the receptors are inhibited by α-bungarotoxin while others are insensitive (Schloβ et al. 1988). In addition, the acetylcholine receptors are the molecular point of attack for important natural (e.g. nicotine) and synthetic insecticides (e.g. chloronicotinyls).
The gene sequences of a number of insect nicotinic acetylcholine receptors are already known. Thus, the sequences of five different subunits have been described in Drosophila melanogaster (Bossy et al. 1988, Hermanns-Borgmeyer et al. 1986, Sawruk et al. 1990a, 1990b, Schulz et al. Unpublished, EMBL accession number Y15593), while five have likewise been described in Locusta migratoria (Stetzer et al. unpublished, EMBL accession numbers AJ000390-AJ000393), one has been described in Schistocerca gregaria (Marshall et al. 1990), two have been described in Myzus persicae (Sgard et al. unpublished, EMBL accession number X81887 and X81888), and one has been described in Manduca sexta (Eastham et al. 1997). Furthermore, a number of partial gene sequences from Drosophila melanogaster have been characterized as so-called expressed sequence tags (Genbank accession numbers AA540687, AA698155, AA697710, AA697326). The fact that individual sequences are very similar to those from other insects suggests that these subunits are functional homologues.